Apparatus and method for bioelectric stimulation, healing acceleration, pain relief, or pathogen devitalization

• US 7,117,034 B2
• Filed: 06/24/2004
• Issued: 10/03/2006
• Est. Priority Date: 06/24/2003
• Status: Active Grant

• Current Assignee: Healthonics, Inc.
• Original Assignee: Healthonics, Inc.
• Inventors: Kronberg, James W.
• Primary Examiner(s): LAYNO, CARL HERNANDZ
• Application Number:
  US10/875,801
• Publication Number:
  US 20040267333A1
• Time in Patent Office: 831 Days
• Field of Search: 607/4, 607/5, 607 68- 70
• US Class Current: 607/2
• CPC Class Codes: A61N 1/025 Digital circuitry features of electrotherapy devices, e.g. memory, clocks, processors
• CPC Class Codes: A61N 1/326 for promoting growth of cells, e.g. bone cells
• CPC Class Codes: A61N 1/36021 for treatment of pain
• CPC Class Codes: A61N 1/36071 Pain

Abstract

An method and method for generating an electrical signal for use in biomedical applications, including two timing-interval generators, each optionally driving a multistep sequencer; analog, digital or hybrid means for combining the resulting timed signals into a complex electrical signal; optional filtering means for blocking direct current, removing selected frequency components from the resulting signal, and/or providing voltage step-up if needed; and conductive means for coupling the resulting signal to a human or animal body, food, beverage or other liquid, cell or tissue culture, or pharmaceutical material, in order to relieve pain, stimulate healing or growth, enhance the production of specific biochemicals, or devitalize selected types of organisms.

Claims

1. An apparatus for generating an electrical signal for use in biomedical applications said apparatus comprising

(a) a first frequency generator that generates a first intermediate output, said first intermediate output being coupled to and thereby controlling

(b) a second frequency generator that generates one or more second intermediate outputs, said second intermediate outputs being coupled to

(c) one or more active or passive electrical components that modify said second intermediate outputs thereby producing one or more third intermediate outputs, said third intermediate outputs being coupled to and thereby controlling one or more logic-level drivers that generate one or more fourth intermediate outputs, said fourth intermediate outputs being coupled to an output filter that generates a final output, said final output constituting said electrical signal comprising:

(i) at least four relatively longer primary timing intervals T₁, T₂, T₃, T₄ and others if present, forming in succession a repeating primary cycle, said primary cycle having a first frequency;

(ii) at least two relatively shorter secondary timing intervals t₁, t₂ and so forth, into which at least one of said primary timing intervals is divided and which form in succession a repeating secondary cycle throughout its length, said secondary cycle having a second frequency, said second frequency being less than about 200 kHz;

while at least one other of said primary timing intervals is not so divided;

(iii) a plurality of substantially constant voltage or current levels L₁, L₂ and so forth;

(iv) selection of one of said voltage or current levels during each of said secondary intervals within a said primary interval which is so divided, or during the whole of said primary interval if it is not so divided;

said levels, selected in succession throughout the course of said primary cycle, thereby forming said electrical signal; and

(v) further selection of one or more of said primary intervals, said further selected intervals being not so divided, as one or more equalizing pulses for the establishment of substantial charge balance throughout the course of any one repetition of said primary cycle,

wherein the selection of said primary and secondary timing intervals, and of said voltage or current levels within each, cause said electrical signal to emulate a specific, defined mathematical function having an amplitude which varies with time, and

wherein said biomedical application comprises pain relief, stimulation of tissue growth, acceleration of tissue healing, stimulation of bone growth, acceleration of bone healing, improvement of bone healing, improvement of bone density, reduction of tissue inflammation, repair of tissue damage, reduction of tissue swelling, promotion of tissue graft survival, promotion of tissue graft survival, modification of blood flow, enhancement of biochemical production, enhancement of tissue biochemical production, devitalization of organisms, enhancement of joint repair, enhancement of joint replacement, enhancement of blood storage, and improvement of neurological conditions.

2. The apparatus as recited in claim 1 further comprising a sequential switch that couples said first intermediate output to said second frequency generator.

3. The apparatus as recited in claim 1 further comprising one or more switches that couple said second intermediate output to said one or more electrical components, said electrical components being active or passive.

4. The apparatus as recited in claim 1 wherein the apparatus may be used to relieve pain, improve sensation, or improve neural function due to one or more of the following:

trauma, surgery, nerve irritation, muscle spasm, trapped nerves, compressed nerves, diabetic neuropathy, peripheral neuropathy, autonomic neuropathy, peripheral vascular disease, plantar fasciitis, low back pain, patella femoral pain.

5. The apparatus as recited in claim 1 wherein the electrical signal generated comprises a waveform comprising at least five primary timing intervals including a zero interval (80), followed by a plurality of high frequency intervals (82a), (82b), (82c) and at least one undivided interval (84).

6. The apparatus as recited in claim 5, wherein the user of said apparatus can select one of said electrical signals to be generated.

7. The apparatus as recited in claim 1 wherein the electrical signal generated comprises a waveform comprising at least four primary timing intervals that include a zero interval (80) and three high frequency intervals (42a), (42b) and (42c).

8. The apparatus as recited in claim 7, wherein the user of said apparatus can select one of said electrical signals to be generated.

9. The apparatus as recited in claim 1 wherein the electrical signal generated comprises a waveform comprising at least four primary timing intervals that include a zero interval (80) and three high frequency intervals (44a), (44b) and (44c).

10. The apparatus as recited in claim 9, wherein the user of said apparatus can select one of said electrical signals to be generated.

11. The apparatus as recited in claim 1 wherein the electrical signal generated comprises a waveform comprising at least eight primary timing intervals that include a zero interval (80) and seven high frequency intervals (46a), (46b), (46c), (46d), (46e), (46f) and (46g).

12. The apparatus as recited in claim 11, wherein the user of said apparatus can select one of said electrical signals to be generated.

13. The apparatus as recited in claim 1 wherein the electrical signal generated comprises a waveform comprising at least ten primary timing intervals that include a first zero interval (80), followed by a first high frequency interval (48a), followed by a second zero interval (80), and a second high frequency interval (48b) followed by a third zero interval (80) and a third high frequency interval (48c) followed by a fourth zero interval (80) and a fourth high frequency interval (48d) followed by a fifth zero interval (80) and a fifth high frequency interval (48e).

14. The apparatus as recited in claim 13, wherein the user of said apparatus can select one of said electrical signals to be generated.

15. The apparatus as recited in claim 1 wherein the electrical signal generated comprises a waveform comprising at least six primary timing intervals that include a zero interval (80), and five high frequency intervals (70a), (70b), (70c), (70d), and (70e).

16. The apparatus as recited in claim 15, wherein the user of said apparatus can select one of said electrical signals to be generated.

17. The apparatus as recited in claim 1 wherein the electrical signal generated comprises a waveform comprising at least six primary timing intervals that include a first zero interval (80), a first high frequency interval (72a), followed by a first undivided interval (72b) followed by a second zero interval (80), followed by a second high frequency interval (72c) and a second undivided interval (72d).

18. The apparatus as recited in claim 17, wherein the user of said apparatus can select one of said electrical signals to be generated.

19. The apparatus as recited in claim 1 wherein the electrical signal generated comprises a waveform comprising at least four primary timing intervals that include a first zero interval (80), followed by a first high frequency interval (74a) followed by a second zero interval (80 ) followed by a second high frequency interval (74b).

20. The apparatus as recited in claim 19, wherein the user of said apparatus can select one of said electrical signals to be generated.

21. The apparatus as recited in claim 1, wherein (a) said electrical signal within any given primary timing interval has both an A.C. and a D.C. amplitude either of which may be zero, and (b) said A.C. amplitude within said primary timing interval, if not zero, results from the presence of a said secondary timing cycle.

22. The apparatus as recited in claim 21, wherein (b) said A.C. amplitude has an amplitude of zero in at least one of said primary timing intervals, and (c) said A.C. amplitude has a nonzero amplitude in at least one other of said primary timing intervals.

23. The apparatus as recited in claim 22, wherein:

(a) a first said primary timing interval T₁ has a single voltage or current level L₁ selected throughout, resulting in a zero A.C. amplitude;

(b) a second said primary timing interval T₂ is divided into said secondary intervals t₁, t₂ and so forth, forming said secondary cycle throughout the length of primary interval T₂, said secondary cycle undergoing a plurality of complete repetitions within said primary interval, one of levels L₁, L₂ and so forth being selected for each of secondary intervals t₁, t₂ and so forth, resulting in a nonzero A.C. amplitude;

(c) a third said primary timing interval T₃, (d) a fourth said primary timing interval T₄, and each said primary timing interval T_5, T₆ and so forth, if present, may either contain a single, constant voltage or current level in the manner of T₁, or be subdivided in the manner of interval T_2;

(e) each said secondary interval or undivided primary interval within said primary cycle has a uniquely assigned voltage or current level, from among L₁, L₂ and so forth, which is always selected when that interval recurs; and

therefore, (f) said electrical signal is substantially identical between any two repetitions of said primary cycle.

24. The apparatus as recited in claim 23, wherein said substantially constant voltage or current levels L₁, L₂ and so forth take the form of constant current levels lying within the range between +10.0 and −

10.0 milliamperes.

25. The apparatus as recited in claim 23, wherein said primary cycle comprises two longest primary timing intervals T_A and T_B, having the relationship 2T_A≦

T_B≦

20T_A where T_B is the longest primary interval and T_A is the second longest, thereby yielding an asymmetric primary cycle with a duty cycle between 66% and 95%.

26. The apparatus as recited in claim 23, wherein at least two of said at least four primary timing intervals differ in length and contain secondary cycles which also differ in frequency.

27. The apparatus as recited in claim 23, wherein said secondary cycle comprises exactly two of said secondary timing intervals t₁ and t₂, having the relationship 2t_A≦

t_B≦

20t_A where t_A may be either of said secondary timing intervals while t_B is the other, thereby yielding an asymmetric secondary cycle with a duty cycle between 66% and 95%.

28. The apparatus as recited in claim 23, wherein said secondary cycle comprises more than two of said secondary timing intervals t₁, t₂, t₃ and so forth.

29. The apparatus as recited in claim 23, wherein said electrical signal is automatically turned off after a preselected period of time.

30. The apparatus as recited in claim 23, comprising:

(a) generating said plurality of primary timing intervals T₁, T₂ and so forth, thereby forming said repeating primary cycle;

(b) generating said plurality of secondary timing intervals t₁, t₂ and so forth, thereby forming said repeating secondary cycle during said at least one primary interval which is so divided;

(c) selecting among said plurality of constant voltage or current levels L₁, L₂ and so forth, one for each of said secondary intervals within a said primary interval which is so divided, or the whole of said primary interval if it is not so divided, thereby forming said electrical signal; and

(d) conductive material for applying said electrical signal to living or nonliving materials.

31. The apparatus as recited in claim 30, further comprising a filter for removing unwanted components from said electrical signal.

32. The apparatus as recited in claim 30, wherein at least one of said generation of said plurality of primary timing intervals or said plurality of secondary timing intervals, thereby forming said repeating primary cycle or said repeating secondary cycle, includes a multistep sequencer.

33. The apparatus as recited in claim 30, wherein said electrical signal is periodic and in which said primary and secondary timing intervals have approximately the magnitudes and relationships:

(a) 50 μ

sec≦

(T₁, T₂, . . . )≦

30 sec;

(b) 200 μ

sec≦

(T₁+T₂+ . . . ) ≦

120 sec;

(c) 2.55 μ

sec (t₁, t₂, . . . )≦

50 msec;

(d) 5 μ

sec≦

(t_a+t_b+ . . . ) 0.5 T_A;

(e) (t_x, t_y, . . . ) ≦

2(t_a+t_b+ . . . ); and

(f) where (T₁, T₂, . . . ), (T₁+T₂+ . . . ), T_A, (t₁, t₂), (t_a+t_b+ . . . ) and (t_x, t_y, . . . ) are as defined in the specification.

34. The apparatus as recited in claim 33, configured to generate four said primary intervals T₁, T₂, T₃ and T₄, a plurality of said secondary intervals t₁, t₂ and so forth, and three said voltage or current levels L₁, L₂ and L₃, such that:

(a) L₁ is substantially zero;

(b) L₂ and L₃ have substantially equal magnitudes but opposite polarities;

(c) T₁ is spent at a constant L_1;

and (d) T₂, T₃ and T₄ all contain secondary timing cycles.

35. The apparatus as recited in claim 34, wherein:

(a) T₁ is the shortest of said primary intervals T₁, T₂, T₃ and T₄;

(b) T₂ and T₄ are roughly equal in length;

(c) T₃ is longer than either T₂ or T₄; and

(d) the A.C. amplitude produced by said secondary timing cycle within T₂ and T₄ is reduced below that produced by said secondary timing cycle within T₃.

36. The apparatus as recited in claim 35, wherein:

(a) the repetition rate of said primary timing cycle may be varied, continuously or stepwise, across some portion of the range from 1 Hz to 500 Hz in order to suit the desired application; and

(b) the repetition rates of said secondary timing cycles within T₂, T₃ and T₄ are substantially equal and lie in the range between 1000 Hz to 200 kHz.

37. The apparatus as recited in claim 35, wherein said amplitude reduction of the signal during T₂ and T₄, below that during T₃, is achieved, in whole or in part, through the selection of at least one said voltage or current level during T₃ which is not used during either T₂ or T₄.

38. The apparatus as recited in claim 35, wherein said amplitude reduction of the signal during T₂ and T₄, below that during T₃, is achieved, in whole or in part, through the use of a different said secondary timing cycle during T₃ from that which is used during either T₂ or T₄.

39. The apparatus as recited in claim 33, configured to generate a plurality P of at least four of said primary timing intervals T₁, T₂, T₃ and so forth, an even number S of said secondary timing intervals t₁, t₂, t₃ and so forth, and an odd number Q of said voltage or current levels L₁, L₂, L₃ and so forth, such that:

(a) L₁ is substantially zero;

(b) The remaining said voltage and current levels L₂, L₃ and so forth form at least one pair such as L_X, L_Y, the members of each said pair being equal in magnitude but opposite in polarity;

(c) T₁ is spent at a constant L₁;

(d) all other said primary timing intervals T₂, T₃ and so forth contain secondary cycles all having substantially equal repetition rates;

(e) a maximum signal amplitude is present during a primary timing interval T_N, where N preferably equals about P/2+1; and

(f) during the remaining said primary intervals, said signal amplitudes increase progressively from T₁ to T_N going either forward or backward around said primary timing cycle, thereby approximating a sinusoidal envelope with its maximum during T_N and minimum during T₁.

40. The apparatus as recited in claim 33, configured to generate any number of said primary timing intervals T₁, T₂, T₃ and so forth, two said secondary timing intervals t₁ and t₂, and three said voltage or current levels L₁, L₂ and L₃, such that:

(a) L₁ is substantially zero;

(b) L₂ and L₃ have substantially equal magnitudes but opposite polarities; and

(c) primary intervals are grouped in threes, wherein (1) the first said primary timing interval in each said group, such as T₁, T₄, T₇ and so forth, are spent at a constant L₁;

(2) the second said primary timing interval in each said group, such as T₂, T₅, T₈ and so forth, contains a said secondary timing cycle alternating between L₂ during t₁ and L₃ during t₂, thereby forming a square- or rectangular-wave signal within each such said even-numbered primary interval; and

(3) the third said primary timing interval in each said group, such as T₃, T₆, T₉ and so forth, is spent at a constant voltage or current level which differs from L₁ thereby forming an equalizing pulse.

41. The apparatus as recited in claim 40, wherein the sum of D.C. amplitudes throughout the primary timing cycle is zero, so that the resulting said electrical signal is charge-balanced.

42. The apparatus as recited in claim 41, wherein (a) said second primary timing interval in each said group contains a rectangular wave having a non-zero D.C. amplitude, and (b) said third primary timing interval in each said group has an opposite D.C. amplitude, causing said electrical signal to be substantially charge-balanced.

43. The apparatus as recited in claim 40, wherein said second and third primary timing intervals within at least one of said groups of three have opposite polarities from those in at least one other of said groups of three.

44. The apparatus as recited in claim 43, wherein (a) at least one of said third primary timing intervals, within at least one of said groups of three, and forming an equalizing pulse, is too short to fully achieve charge balance;

and (b) charge balance instead is achieved, in whole or in part, through polarity reversal between at least one of said second primary timing intervals, and at least one other of said second primary timing intervals, within said groups of three.

45. The apparatus as recited in claim 40, wherein at least one of said second primary timing intervals, within at least one of said groups of three, contains a secondary timing cycle whose repetition rate differs from that in at least one other of said second primary timing intervals.

46. The apparatus as recited in claim 37, further comprising a switch whereby the primary timing intervals, secondary timing intervals, voltage or current levels, or any combination of these may be altered so as to produce any of a plurality of the electrical signals already described, upon demand.

47. The apparatus as recited in claim 46, wherein said selection comprises:

(a) the electrical signal as recited in claim 39;

or (b) the electrical signal as recited in claim 42.

48. The apparatus as recited in claim 30, in which said electrical signal is aperiodic and in which said primary and secondary timing intervals have approximately the magnitudes and relationships:

(a) 50 μ

sec≦

(T₂, T₃, . . . )≦

30 sec, (b) 200 μ

sec≦

(T₂+T₃+ . . . ) ≦

120 sec, (c) 2.55 μ

sec≦

(t₁, t₂, . . . )≦

50 msec, (d) 5 μ

sec≦

(t_a+t_b+ . . . )≦

0.5 T_A, and (e) (t_x, t_y, . . . )≦

2(t_a+t_b+ . . . ), where T₁ may be arbitrarily long, and where (T₂, T₃, . . . ), (T₂+T₃+ . . . ), T_A, (t₁, t₂, . . . ), (t_a+t_b+ . . . ) and (t_x, t_y, . . . ) are as defined in the specification.

49. The apparatus as recited in claim 48, configured to generate any number P of said primary timing intervals T₁, T₂, T₃ and so forth, an even number S of said secondary timing intervals t₁, t₂, t₃ and so forth, and an odd number Q of said voltage or current levels L₁, L₂, L₃ and so forth, such that:

(a) L₁ is substantially zero;

(b) the remaining said voltage and current levels L₂, L₃ and so forth form at least one pair such as L_X, L_Y, the members of each said pair being equal in magnitude but opposite in polarity;

(c) T₁ is spent at a constant L₁;

(d) all other said primary timing intervals T₂, T₃ and so forth contain secondary cycles all having substantially equal repetition rates;

(e) a maximum signal amplitude is present during T₂; and

(1) during the remaining said primary intervals, said signal amplitudes decrease progressively with time throughout said primary timing cycle, thereby approximating an exponentially-decaying envelope with its maximum during T₂ and minimum during T_P.

50. The apparatus as recited in claim 49, wherein each iteration of the primary timing cycle is initiated by an external signal.

51. The apparatus as recited in claim 30, wherein said electrical signal is applied by conductive material to a human or animal body, isolated tissue or cell culture in order to relieve pain, stimulate healing, or increase cell metabolism, proliferation, differentiation, or production of desired substances or reduction of undesirable substances.

52. The apparatus as recited in claim 51, wherein said conductive material constitutes a plurality of flat bodies of electrically-conductive material applied directly to the skin surface.

53. The apparatus as recited in claim 51, wherein said conductive material includes at least one body of electrically-conductive material applied to a tissue surface other than the skin.

54. The apparatus as recited in claim 51, wherein said conductive material includes at least one body of electrically-conductive material inserted into or implanted within a human or animal body or tissue.

55. The apparatus as recited in claim 51, wherein said conductive material includes at least one body of electrically-conductive material wholly or partially immersed in an electrically-conductive liquid.

56. The apparatus as recited in claim 51, wherein said conductive material include a body of electrically-conductive liquid in which a human or animal body or tissue, or part thereof, may be immersed.

57. The apparatus as recited in claim 30, wherein said electrical signal is applied by conductive material to a human or animal body, isolated tissue or cell culture, food, beverage or other material in order to devitalize selected pathogenic organisms which may be present.

97. The method as recited in claim 57, wherein said amplitude reduction of the signal during T₂ and T₄, below that during T₃, is achieved, in whole or in part, through the selection of at least one said voltage or current level during T₃ which is not used during either T₂ or T₄.

58. An apparatus for generating an electrical signal for use in biomedical applications, said apparatus comprising (a) a first frequency generator that generates a first intermediate output, said first intermediate output being coupled to and thereby controlling (b) a second frequency generator that generates one or more second intermediate outputs, said second intermediate outputs being coupled to (c) one or more active or passive electrical components that modify said second intermediate outputs thereby producing one or more third intermediate outputs, said third intermediate outputs being coupled to and thereby controlling one or more logic-level drivers that generate one or more fourth intermediate outputs, said fourth intermediate outputs being coupled to an output filter that generates a final output, said final output constituting said electrical signal comprising:

(a) at least four relatively longer primary timing intervals T₁, T₂, T₃, T₄ and others if present, forming in succession a repeating primary cycle, said primary cycle having a frequency;

(b) at least two relatively shorter secondary timing intervals t₁, t₂ and so forth, into which at least one of said primary timing intervals is divided and which form in succession a repeating secondary cycle throughout its length, said secondary cycle having a frequency, said frequency lying below 200 kHz;

while at least one other of said primary timing intervals is not so divided;

(c) a plurality of substantially constant voltage or current levels L₁, L₂ and so forth;

(d) selection of one of said voltage or current levels during each of said secondary intervals within a said primary interval which is so divided, or during the whole of said primary interval if it is not so divided;

said levels, selected in succession throughout the course of said primary cycle, thereby forming said electrical signals

wherein the selection of said primary and secondary timing intervals, and of said voltage or current levels within each, cause said electrical signal to emulate a specific, defined mathematical function having an amplitude which varies with time, and

wherein said biomedical application comprises pain relief, stimulation of tissue growth, acceleration of tissue healing, stimulation of bone growth, acceleration of bone healing, improvement of bone healing, improvement of bone density, reduction of tissue inflammation, repair of tissue damage, reduction of tissue swelling, promotion of tissue graft survival, promotion of tissue graft survival, modification of blood flow, enhancement of biochemical production, enhancement of tissue biochemical production, devitalization of organisms, enhancement of joint repair, enhancement of joint replacement, enhancement of blood storage, and improvement of neurological conditions.

59. The apparatus as recited in claims or 58 wherein said biomedical applications further comprise treatment of rotator cuff injury, treatment of osteoarthritis, treatment of carpal tunnel syndrome.

60. A method for generating an electrical signal for use in biomedical applications said, method comprising:

(a) generating at least four relatively longer primary timing intervals T₁, T₂, T₃, T₄ and others if present, forming in succession a repeating primary cycle, said primary cycle having a frequency;

(b) generating at least two relatively shorter secondary timing intervals t₁, t₂ and so forth, into which at least one of said primary timing intervals is divided and which form in succession a repeating secondary cycle throughout its length, said secondary cycle having a frequency, said frequency lying below 200 kHz;

while at least one other of said primary timing intervals is not so divided;

(c) generating a plurality of substantially constant voltage or current levels L₁, L₂ and so forth;

(d) selecting one of said voltage or current levels during each of said secondary intervals within a said primary interval which is so divided, or during the whole of said primary interval if it is not so divided;

said levels, selected in succession throughout the course of said primary cycle, thereby forming said electrical signal;

(e) further selecting one or more of said primary intervals, said further selected intervals being not so divided, as one or more equalizing pulses for the establishment of substantial charge balance throughout the course of any one repetition of said primary cycle; and

(f) applying said electrical signal to one or more of the following;

human body, animal body, cell culture, tissue culture, food, liquid, and pharmaceutical materials,

wherein the selection of said primary and secondary timing intervals, and of said voltage or current levels within each, cause said electrical signal to emulate a specific, defined mathematical function having an amplitude which varies with time, and

wherein said biomedical application comprises pain relief, stimulation of tissue growth, acceleration of tissue healing, stimulation of bone growth, acceleration of bone healing, improvement of bone healing, improvement of bone density, reduction of tissue inflammation, repair of tissue damage, reduction of tissue swelling, promotion of tissue graft survival, promotion of tissue graft survival, modification of blood flow, enhancement of biochemical production, enhancement of tissue biochemical production, devitalization of organisms, enhancement of joint repair, enhancement of joint replacement, enhancement of blood storage, and improvement of neurological conditions.

61. The method as recited in claim 60, further comprising filtering said electrical signal to remove unwanted components.

62. The method as recited in claim 60, wherein said electrical signal is applied by said conductive material to a human or animal body, isolated tissue or cell culture, food, beverage or other material to inactivate selected pathogenic organisms which may be present.

63. The method as recited in claim 60 wherein the method may be used to relieve pain, improve sensation, or improve neural function due to one or more of the following:

trauma, surgery, nerve irritation, muscle spasm, trapped nerves, compressed nerves, diabetic neuropathy, peripheral neuropathy, autonomic neuropathy, peripheral vascular disease, plantar fasciitis, low back pain, patella femoral pain.

64. The method as recited in claim 60 wherein the electrical signal generated comprises a waveform comprising at least five primary timing intervals including a zero interval (80), followed by a plurality of high frequency intervals (82a), (82b), (82c) and at least one undivided interval (84).

65. The method as recited in claim 60 wherein the electrical signal generated comprises a waveform comprising at least four primary timing intervals that include a zero interval (80) and three high frequency intervals (42a), (42b) and (42c).

66. The method as recited in claim 60 wherein the electrical signal generated comprises a waveform comprising at least four primary timing intervals that include a zero interval (80) and three high frequency intervals (44a), (44b) and (44c).

67. The method as recited in claim 60 wherein the electrical signal generated comprises a waveform comprising at least eight primary timing intervals that include a zero interval (80) and seven high frequency intervals (46a), (46b), (46c), (46d), (46e), (46f) and (46g.

68. The method as recited in claim 60 wherein the electrical signal generated comprises a waveform comprising at least ten primary timing intervals that include a first zero interval (80), followed by a first high frequency interval (48a), followed by a second zero interval (80), and a second high frequency interval (48b) followed by a third zero interval (80) and a third high frequency interval (48c) followed by a fourth zero interval (80) and a fourth high frequency interval (48d) followed by a fifth zero interval (80) and a fifth high frequency interval (48e).

69. The method as recited in claim 60 wherein the electrical signal generated comprises a waveform comprising at least six primary timing intervals that include a zero interval (80), and five high frequency intervals (70a), (70b), (70c), (70d), and (70e).

70. The method as recited in claim 60 wherein the electrical signal generated comprises a waveform comprising at least six primary timing intervals that include a first zero interval (80), a first high frequency interval (72a), followed by a first undivided interval (72b) followed by a second zero interval (80), followed by a second high frequency interval (72c) and a second undivided interval (72d).

71. The method as recited in claim 60 wherein the electrical signal generated comprises a waveform comprising at least four primary timing intervals that include a first zero interval (80), followed by a first high frequency interval (74a) followed by a second zero interval (80) followed by a second high frequency interval (74b).

72. The method as recited in claim 60, wherein a multistep sequencer is used to help generate said primary timing intervals T₁, T₂ and so forth, forming said repeating primary cycle.

73. The method as recited in claim 72, wherein the outputs of said multistep sequencer determine the relative lengths of said primary timing intervals.

74. The method as recited in claim 60, wherein a multistep sequencer is used to help generate said secondary timing intervals t₁, t₂ and so forth, forming said repeating secondary cycle.

75. The method as recited in claim 74, wherein the outputs of said multistep sequencer determine the relative lengths of said secondary timing intervals.

76. The method as recited in claim 60, in which said electrical signal is aperiodic and in which said primary and secondary timing intervals have approximately the magnitudes and relationships:

(a) 50 μ

sec (T₂, T₃, . . . )≦

30 sec, (b) 200 μ

sec≦

(T₂+T₃+ . . . )≦

120 sec, (c) 2.5 μ

sec≦

(t₁, t₂, . . . ) ≦

50 msec, (d) 5 μ

sec≦

(t_a+t_b+ . . . )≦

0.5T_A, and (e) (t_x, t_y, . . . )≦

2(t_a+t_b+ . . . ), where T₁ may be arbitrarily long, and where (T₂, T₃, . . . ), (T₂+T₃+ . . . ), T_A, (t₁, t₂, . . . ), (t_a+t_b. . . ) and (t_x, t_y, . . . ) are as defined in the specification.

77. The method as recited in claim 76, wherein are generated any number P of said primary timing intervals T₁, T₂, T₃ and so forth, an even number S of said secondary timing intervals t₁, t₂, t₃ and so forth, and an odd number Q of said voltage or current levels L₁, L₂, L₃ and so forth, such that:

(a) L₁ is substantially zero;

(b) the remaining said voltage and current levels L₂, L₃ and so forth form at least one pair such as L_X, L_Y, the members of each said pair being equal in magnitude but opposite in polarity;

(c) T₁ is spent at a constant L₁;

(d) all other said primary timing intervals T₂, T₃ and so forth contain secondary cycles all having substantially equal repetition rates;

(e) a maximum signal amplitude is present during T₂; and

(f) during the remaining said primary intervals, said signal amplitudes decrease progressively with time throughout said primary timing cycle, thereby approximating an exponentially-decaying envelope with its maximum during T₂ and minimum during T_P.

78. The method as recited in claim 77, wherein each iteration of the primary timing cycle is initiated by an external signal.

79. The method as recited in claim 60, wherein said electrical signal is applied by conductive material to a human or animal body, isolated tissue or cell culture to relieve pain, stimulate healing, or increase cell metabolism, proliferation, differentiation, or production of desired substances or reduction of undesirable substances.

80. The method as recited in claim 79, wherein said conductive material constitutes a plurality of flat bodies of electrically-conductive material applied directly to the skin surface.

81. The method as recited in claim 79, wherein said conductive material includes at least one body of electrically-conductive material applied to a tissue surface other than the skin.

82. The method as recited in claim 79, wherein said conductive material includes at least one body of electrically-conductive material inserted into or implanted within a human or animal body or tissue.

83. The method as recited in claim 79, wherein said conductive material includes at least one body of electrically-conductive material wholly or partially immersed in an electrically-conductive liquid.

84. The method as recited in claim 79, wherein said conductive material includes a body of electrically-conductive liquid in which a human or animal body or tissue, or part thereof, may be immersed.

85. The method as recited in claim 60, wherein:

(a) said electrical signal within any given primary timing interval has both an A.C. and a D.C. amplitude either of which may be zero, and (b) said A.C. amplitude within said primary timing interval, if not zero, results from the presence of a said secondary timing cycle.

86. The method as recited in claim 85, wherein:

(b) said A.C. component has an amplitude of zero in at least one of said primary timing intervals, and (c) said A.C. component has a nonzero amplitude in at least one other of said primary timing intervals.

87. The method as recited in claim 86, wherein:

(a) first said primary timing interval T₁ has a single voltage or current level L₁ selected throughout, resulting in a zero A.C. amplitude;

(b) second said primary timing interval T₂ is divided into said secondary intervals t₁, t₂ and so forth, forming said secondary cycle throughout the length of primary interval T₂, said secondary cycle undergoing a plurality of complete repetitions within said primary interval, one of levels L₁, L₂ and so forth being selected for each of secondary intervals t₁, t₂ and so forth, resulting in a nonzero A.C. amplitude;

(c) third said primary timing interval T₃, fourth said primary timing interval T₄, and each said primary timing interval T₅, T₆ and so forth, if present, may either contain a single, constant voltage or current level in the maimer of T₁, or be subdivided in the maimer of interval T₂;

(d) each said secondary interval or undivided primary interval within said primary cycle has a uniquely assigned voltage or current level, from among L₁, L₂ and so forth, which is always selected when that interval recurs; and

therefore, (e) said electrical signal is substantially identical between any two repetitions of said primary cycle.

88. The method as recited in claim 87, wherein said substantially constant voltage or current levels L₁, L₂ and so forth take the form of constant current levels +10.0 and −

10.0 milliamperes.

89. The method as recited in claim 88, wherein said primary cycle comprises two longest primary timing intervals T_A and T_B, having the relationship 2T_A≦

T_B≦

20T_A where T_B is the longest primary interval and T_A is the second longest, thereby yielding an asymmetric primary cycle with a duty cycle between 66% and 95%.

90. The method as recited in claim 88, wherein at least two of said at least four primary timing intervals differ in length and contain secondary cycles which also differ in frequency.

91. The method as recited in claim 87, wherein said secondary cycle comprises exactly two said secondary timing intervals t₁ and t₂, having the relationship 2t_A≦

t_B≦

20t_A where t_A may be either of said secondary timing intervals while t_B is the other, thereby yielding an asymmetric secondary cycle with a duty cycle between 66% and 95%.

92. The method as recited in claim 87, wherein said electrical signal is automatically turned off after a preselected period of time.

93. The method as recited in claim 60, wherein said electrical signal is periodic and in which said primary and secondary timing intervals have approximately the magnitudes and relationships:

(a) 50 μ

sec≦

(T₁, T₂, . . . )≦

30 sec;

(b) 200 μ

sec≦

(T₁+T₂+ . . . ) ≦

120 sec;

(c) 2.5 μ

sec (t₁, t₂, . . . )≦

50 msec;

(d) 5 μ

sec≦

(t_a+t_b+. . . )≦

0.5T_A; and

(e) (t_x, t_y. . . ) ≦

2(t_a+t_b+. . . );

where (T₁, T₂, . . . ), (T₁+T₂+ . . . ), T_A, (t₁, t₂, . . . ), (t_a+t_b. . . ) and (t_x, t_y, . . . ) are as defined in the specification.

94. The method as recited in claim 93, wherein are generated four said primary intervals T₁, T₂, T₃ and T₄, a plurality of said secondary intervals t₁, t₂ and so forth, and three said voltage or current levels L₁, L₂ and L₃, such that:

(a) L₁ is substantially zero;

(b) L₂ and L₃ have substantially equal magnitudes but opposite polarities;

(c) T₁ is spent at a constant L₁; and

(d) T₂, T₃ and T₄ all contain secondary timing cycles.

95. The method as recited in claim 94, wherein:

(a) T₁ is the shortest of said primary intervals T₁, T₂, T₃ and T₄;

(b) T₂ and T₄ are roughly equal in length;

(c) T₃ is longer than either T₂ or T₄; and

(d) the A.C. amplitude produced by said secondary timing cycle within T₂ and T₄ is reduced below that produced by said secondary timing cycle within T₃.

96. The method as recited in claim 95, wherein:

(a) the repetition rate of said primary timing cycle may be varied, continuously or stepwise, across some portion of the range from 1 Hz to 500 Hz in order to suit the desired application; and

(b) the repetition rates of said secondary timing cycles within T₂, T₃ and T₄ are substantially equal and lie in the range between approximately 1000 Hz and 200 kHz.

98. The method as recited in claim 95, wherein said amplitude reduction of the signal during T₂ and T₄, below that during T₃, is achieved, in whole or in part, through the use of a different said secondary timing cycle during T₃ from that which is used during either T₂ or T₄.

99. The method as recited in claim 93, wherein are generated a plurality P of at least four of said primary timing intervals T₁, T₂, T₃ and so forth, an even number S of said secondary timing intervals t₁, t₂, t₃ and so forth, and an odd number Q of said voltage or current levels L₁, L₂, L₃ and so forth, such that:

(a) L₁ is substantially zero;

(b) The remaining said voltage, and current levels L₂, L₃ and so forth form at least one pair such as L_X, L_Y, the members of each said pair being equal in magnitude but opposite in polarity;

(c) T₁ is spent at a constant L₁;

(d) all other said primary timing intervals T₂, T₃ and so forth contain secondary cycles all having substantially equal repetition rates;

(e) a maximum signal amplitude is present during a primary timing interval T_N, where N preferably equals about P/2+1; and

(f) during the remaining said primary intervals, said signal amplitudes increase progressively from T₁ to T_N going either forward or backward around said primary timing cycle, thereby approximating a sinusoidal envelope with its maximum during T_N and minimum during T₁.

100. The method as recited in claim 93, wherein are generated any number of said primary timing intervals T₁, T₂, T₃ and so forth, two said secondary timing intervals t₁ and t₂, and three said voltage or current levels L₁, L₂ and L₃, such that:

(a) L₁ is substantially zero;

(b) L₂ and L₃ have substantially equal magnitudes but opposite polarities; and

(c) primary intervals are grouped in threes, wherein (1) the first said primary timing interval in each said group, such as T₁, T₄, T₇ and so forth, are spent at a constant L₁;

(2) the second said primary timing interval in each said group, such as T₂, T₅, T₈ and so forth, contains a said secondary timing cycle alternating between L₂ during t₁ and L₃ during t₂, thereby forming a square- or rectangular-wave signal within each such said even-numbered primary interval; and

(3) the third said primary timing interval in each said group, such as T₃, T₆, T₉ and so forth, is spent at a constant voltage or current level which differs from L₁ thereby forming an equalizing pulse.

101. The method as recited in claim 100, wherein the sum of D.C. amplitudes throughout the primary timing cycle is zero, so that the resulting said electrical signal is charge-balanced.

102. The method as recited in claim 101, wherein:

(a) said second primary timing interval in each said group contains a rectangular wave having a non-zero D.C. amplitude, and (b) said third primary timing interval in each said group has an opposite D.C. amplitude, causing said electrical signal to be substantially charge-balanced.

103. The method as recited in claim 100, wherein said second and third primary timing intervals within at least one of said groups of three have opposite polarities from those in at least one other of said groups of three.

104. The method as recited in claim 100, wherein (a) at least one of said third primary timing intervals, within at least one of said groups of three, and forming an equalizing pulse, is too short to fully achieve charge balance;

and (b) charge balance instead is achieved, in whole or in part, through polarity reversal between at least one of said second primary timing intervals, and at least one other of said second primary timing intervals, within said groups of three.

105. The method as recited in claim 100, wherein at least one of said second primary timing intervals, within at least one of said groups of three, contains a secondary timing cycle whose repetition rate differs from that in at least one other of said second primary timing intervals.

106. The method as recited in claim 60, further comprising the selection of one of a plurality of sets comprising primary timing intervals, secondary timing intervals, voltage or current levels, or any combination of these, so as to produce any of a plurality of the electrical signals already described, upon demand.

107. The method as recited in claim 106, wherein said selection comprises:

(a) the electrical signal as recited in claim 100; and

(b) the electrical signal as recited in claim 102.

108. A method for generating an electrical signal for use in biomedical applications, said method comprising:

(a) generating at least four relatively longer primary timing intervals T₁, T₂, T₃, T₄ and others if present, forming in succession a repeating primary cycle, said primary cycle having a frequency;

(b) generating at least two relatively shorter secondary timing intervals t₁, t₂ and so forth, into which at least one of said primary timing intervals is divided and which form in succession a repeating secondary cycle throughout its length, said secondary cycle having a frequency, said frequency being less than about 200 kHz;

while at least one other of said primary timing intervals is not so divided;

(c) generating a plurality of substantially constant voltage or current levels L₁, L₂ and so forth;

(d) selecting one of said voltage or current levels during each of said secondary intervals within a said primary interval which is so divided, or during the whole of said primary interval if it is not so divided;

said levels, selected in succession throughout the course of said primary cycle, thereby forming said electrical signal; and

(e) applying said electrical signal to one or more of the following;

human body, animal body, cell culture, tissue culture, food, liquid, and pharmaceutical materials

wherein the selection of said primary and secondary timing intervals, and of said voltage or current levels within each, cause said electrical signal to emulate a specific, defined mathematical function having an amplitude which varies with time, and

wherein said biomedical application comprises pain relief, stimulation of tissue growth, acceleration of tissue healing, stimulation of bone growth, acceleration of bone healing, improvement of bone healing, improvement of bone density, reduction of tissue inflammation, repair of tissue damage, reduction of tissue swelling, promotion of tissue graft survival, promotion of tissue graft survival, modification of blood flow, enhancement of biochemical production, enhancement of tissue biochemical production, devitalization of organisms, enhancement of joint repair, enhancement of joint replacement, enhancement of blood storage, and improvement of neurological conditions.

109. The method as recited in claims 60 or 108 wherein said biomedical applications further comprise treatment of rotator cuff injury, treatment of osteoarthritis, treatment of carpal tunnel syndrome.

110. An apparatus comprising a generating assembly constructed and arranged to produce an electrical signal used in biomedical applications said electrical signal comprising (a) a repeating primary cycle, the primary cycle having at least four primary timing intervals, and (b) a repeating secondary cycle formed by dividing at least one of said primary timing intervals into at least two secondary timing intervals, the secondary cycle having a frequency below 200 kHz, each of the secondary intervals within the primary interval which is divided having a substantially constant voltage or current level, or during the whole of the primary interval not divided having a substantially constant voltage or current level, and at least one of the primary timing intervals not divided being an equalizing pulse to substantially charge balance the electrical signal throughout the course of any one repetition of the primary cycle

wherein the selection of said primary and secondary timing intervals, and of said voltage or current levels within each, cause said electrical signal to emulate a specific, defined mathematical function having an amplitude which varies with time, and

wherein said biomedical application comprises pain relief, stimulation of tissue growth, acceleration of tissue healing, stimulation of bone growth, acceleration of bone healing, improvement of bone healing, improvement of bone density, reduction of tissue inflammation, repair of tissue damage, reduction of tissue swelling, promotion of tissue graft survival, promotion of tissue graft survival, modification of blood flow, enhancement of biochemical production, enhancement of tissue biochemical production, devitalization of organisms, enhancement of joint repair, enhancement of joint replacement, enhancement of blood storage, and improvement of neurological conditions.

111. A method of substantially charge balancing an electrical signal used in biomedical applications said method comprising (a) generating a repeating primary cycle, the primary cycle having at least four primary timing intervals, (b) forming a repeating secondary cycle by dividing at least one of said primary timing intervals into a least two secondary timing intervals, the secondary cycle having a frequency below 200 kHz, (c) selecting a substantially constant voltage or current level during each of the secondary intervals within the primary interval which is divided, or during the whole of the primary interval not divided, and (d) substantially charge balancing throughout the course of any one repetition of the primary cycle by selecting at least one of the primary timing intervals not divided as an equalizing pulse,

wherein the selection of said primary and secondary timing intervals, and of said voltage or current levels within each, cause said electrical signal to emulate a specific, defined mathematical function having an amplitude which varies with time, and

wherein said biomedical application comprises pain relief, stimulation of tissue growth, acceleration of tissue healing, stimulation of bone growth, acceleration of bone healing, improvement of bone healing, improvement of bone density, reduction of tissue inflammation, repair of tissue damage, reduction of tissue swelling, promotion of tissue graft survival, promotion of tissue graft survival, modification of blood flow, enhancement of biochemical production, enhancement of tissue biochemical production, devitalization of organisms, enhancement of joint repair, enhancement of joint replacement, enhancement of blood storage, and improvement of neurological conditions.

112. An apparatus for substantially charge balancing an electrical signal used in biomedical applications, said apparatus comprising (a) means for generating a repeating primary cycle, the primary cycle having at least four primary timing intervals, and (b) means for generating a repeating secondary cycle formed by dividing at least one of said primary timing intervals into a least two secondary timing intervals, the secondary cycle having a frequency below 200 kHz, each of the secondary intervals within the primary interval which is divided having a substantially constant voltage or current level, the whole of the primary interval not divided having a substantially constant voltage or current level, and at least one of the primary timing intervals not divided being an equalizing pulse to substantially charge balance the electrical signal throughout the course of any one repetition of the primary cycles

wherein the selection of said primary and secondary timing intervals, and of said voltage or current levels within each, cause said electrical signal to emulate a specific, defined mathematical function having an amplitude which varies with time, and

wherein said biomedical application comprises pain relief, stimulation of tissue growth, acceleration of tissue healing, stimulation of bone growth, acceleration of bone healing, improvement of bone healing, improvement of bone density, reduction of tissue inflammation, repair of tissue damage, reduction of tissue swelling, promotion of tissue graft survival, promotion of tissue graft survival, modification of blood flow, enhancement of biochemical production, enhancement of tissue biochemical production, devitalization of organisms, enhancement of joint repair, enhancement of joint replacement, enhancement of blood storage, and improvement of neurological conditions.

113. An apparatus comprising a processor programmed and connected to produce an electrical signal used in biomedical applications, said electrical signal comprising (a) a repeating primary cycle, the primary cycle having at least four primary timing intervals, and (b) a repeating secondary cycle formed by dividing at least one of said primary timing intervals into at least two secondary timing intervals, the secondary cycle having a frequency below 200 kHz, each of the secondary intervals within the primary interval which is divided having a substantially constant voltage or current level, the whole of the primary interval not divided having a substantially constant voltage or current level, and at least one of the primary timing intervals not divided being an equalizing pulse to substantially charge balance the electrical signal throughout the course of any one repetition of the primary cycle,

wherein said biomedical application comprises pain relief, stimulation of tissue growth, acceleration of tissue healing, stimulation of bone growth, acceleration of bone healing, improvement of bone healing, improvement of bone density, reduction of tissue inflammation, repair of tissue damage, reduction of tissue swelling, promotion of tissue graft survival, promotion of tissue graft survival, modification of blood flow, enhancement of biochemical production, enhancement of tissue biochemical production, devitalization of organisms, enhancement of joint repair, enhancement of joint replacement, enhancement of blood storage, and improvement of neurological conditions.